The oral cavity is constantly exposed to a variety of microbial challenges that lead to bacterially induced periodontal diseases and other infections. Innate host defenses are a critical aspect of maintaining health especially in mucosal sites. Oral epithelial cells from gingiva have been recently shown to express antimicrobial peptides of the beta-defensin family, which are proposed to function as a first line of innate host defense. Expression varies between individuals; those with defects in defensin expression or function may be susceptible to recurrent or opportunistic infection, especially if they are immunocompromised. The goal of this proposal is to identify critical polymorphisms that alter expression or function of beta-defensins, to develop rapid diagnostic screening methods for these polymorphisms, and to test the hypothesis that beta-defensin polymorphisms are associated with oral candidiasis, a common recurrent oral mucosal disorder. The role of these natural antibiotics in oral health and in susceptibility to disease is a new area of research which has implications for understanding disease pathogenesis, genetic susceptibility, normal host defenses, and the relationship of the innate host defenses with inflammation in the oral cavity and elsewhere in the body. The technology being developed in this project will produce commercially valuable diagnostic tests. PROPOSED COMMERCIAL APPLICATION: The genetic polymorphisms identified and the methods for screening to be developed in this project will lead to commercially valuable and innovative diagnostic tests for determining susceptibility to recurrent mucosal infections, thus improving the potential for prevention and treatment.